crossing96/oncoscreening huggingface dataset:
Polymorphism in the N-acetyltransferase 1 alleles NAT1*10 and NAT1*14A and cytological gradings of exfoliated urothelial cells in benzidine-exposed Chinese workers: discussion of ethnic differences.	N-acetyltransferase 1 (NAT1) modifies bladder cancer risk in European populations exposed to aromatic amines in cigarette smoke. The present study was performed to investigate a possible association between NAT1*10 and NAT1*14A genotypes and bladder cancer risk in benzidine-exposed Chinese workers. Based on the cytological gradings of exfoliated urothelial cells according to Papanicolaou, an exposed research cohort was stratified into subgroups. An allele-specific PCR-based procedure was used to detect the polymorphism in the polyadenylation signal at the locus NAT1 T(1088)A. A nested PCR-RFLP procedure was conducted to differentiate NAT1*14A (T(1088)A, C(1095)A, and G(560)A) from NAT1*10 (T(1088)A, C(1095)A). No significantly different frequencies of homozygous and heterozygous NAT1*10 alleles were found among the subgroups with (i) gradings according to Papanicolaou < or = II (18.3 and 40.2%, respectively), (ii) higher gradings according to Papanicolaou (> II; 28.0 and 34.1%, respectively), and (iii) with bladder cancer (26.3 and 34.2%, respectively). The present data show that NAT1*10 neither displayed an association with an elevated grading of urothelial cells nor a clear impact on the risk for bladder cancer in benzidine-exposed Chinese workers. Discrepancies with the findings in European populations could point to ethnic differences in the disposition of aromatic amines.	bladder
Guidelines on diagnosis and treatment of superficial bladder cancer.	This manuscript reviews the guidelines of the European Association of Urology (EAU) on superficial bladder tumors and adds new data which has come available since 2001. It emphasises the data which are evidenced based and clearly explained where still insufficient research is available to make clear recommendations. Intravenous urethrography (IVU) is only necessary in grade 3 tumors. A good transurethral resection (TUR), with muscle in the specimen is essential. Random biopsies are only necessary when there is positive urinary cytology or when tumor in situ (TIS) is suspected. The variability in pathology interpretation remains a problem which seems not to have been solved by the new WHO 1998 classification. A review of pathology seems indicated when aggressive therapy is planned or there is a discrepancy between the visual findings and pathology. The visual judgement of urologists in superficial bladder tumors is very good. Second resection is indicated whenever insufficient material is delivered and in any T1 G3 tumor. In the last infiltrative tumors are regularly found. The treatment largely depends on prognostic parameters. For recurrence rate multiplicity of the tumor is most important, followed by recurrence rate, volume of the tumor, grade and T category. For progression the most important tumor is the anaplasia grade and the T category. Up to 50% of T1 G3 tumors and TIS evaluate to invasive tumors. Even low risk tumors still have an important recurrence rate of at least 20%/year in the first years after diagnosis. One chemo instillation immediately after TUR is indicated in low and intermediate risk superficial bladder tumors. Intravesical chemotherapy prevents recurrence but not progression. Ideal dosage and schedule of instillation is not clearly defined. Longterm therapy is not worthwhile. Bacille Calmette-Guerin (BCG) therapy is indicated in all tumors at high risk for progression. In tumors at high risk for recurrence it is also superior to intravesical chemotherapy, but its side-effects are more pronounced. Local or systemic side-effects are not related to efficacy and side-effects do not increase over time. The ideal schedule for BCG has not yet been found. It is however clear that some kind of maintenance therapy is necessary to obtain good results. BCG failure is probably any tumor which recurs at 3 and 6 months under BCG therapy. One third dose seems as sufficient as a full dose BCG. That BCG can spare the bladder in T1g3 tumors is largely documented but the chance to save the bladder when the tumor is still present after 2 cycles of BCG is very low. Cystectomy is indicated in these BCG failures. Vitamin E, A, and Lactobacillus Casei are probably effective in the prevention of the disease. Stopping smoking is advocated. Cystoscopy is still the gold standard in follow-up. It is advocated at 3 months and thereafter according to the prognostic parameters. High grade tumors are at risk life long. Follow-up of 5 years for low risk tumors seems reasonable.	bladder
[Expression of IGF-I and IGF-IR in bladder cancer].	BACKGROUND & OBJECTIVE: Insulin-like growth factors (IGF) is one of polypeptide growth factors that stimulate proliferation, survival, and differentiation in many cell types; their signal pathways implicate development and progression of many kinds of malignant tumor, while less study were undergone on the roles of IGF-I and IGF-IR in bladder cancer genesis. This study was designed to investigate the expression of IGF-I and IGF-IR and proliferation cell nuclear antigen (PCNA) in human normal and carcinomatous bladder cancer, and to explore the mechanism of IGF-I and IGF-IR in cellular proliferation and tumorigenesis of bladder cancer. METHODS: Immunohistochemical methods were adopted to examine expression of IGF-I, IGF-IR, and PCNA in 88 cases with bladder cancer and 12 cases with normal bladder tissues. The relationship of expression of IGF-I and IGF-IR with various clinicopathological parameters and PCNA were analyzed. RESULTS: The protein expression rates of IGF-I and IGF-IR in bladder cancer were 73.9% and 59.1%, significantly higher than 33.3% and 16.7% in normal tissues, respectively(P< 0.05). Both two protein expression were association with PCNA indexes in bladder cancer (P< 0.05). There were close relationship among IGF-I expression and tumor recurrence (P< 0.05), IGF-IR and tumor grade, stage and recurrence (P< 0.05). CONCLUSION: Abnormality of IGF-I-IGF-IR autocrine loop play an important role in development and progression of bladder cancer by promoting abnormal cellular proliferation. IGF-IR may be a marker for evaluating tumor biological behaviors.	bladder
[Association of uPA and uPAR expression with invasive behaviors of urinary transitional cell carcinoma].	BACKGROUND & OBJECTIVE: Urokinase-type plasminogen activator (uPA)/its receptor (uPAR), serine protease system, plays a key role in the degradation of extracellular matrix and basement membranes, and intensifying the tumor invasion. The study was designed to investigate the expression of uPA and uPAR in urinary transitional cell carcinoma. The correlation between their expression and tumor invasion was evaluated. METHODS: The expression and localization of uPA and uPAR were examined among 50 cases of renal pelvic and ureter carcinoma and 40 cases of bladder cancer using the PicTure(TM) current type of immunohistochemical two-step method. RESULTS: The normal pelvic, ureter, and bladder did not express uPA and uPAR. The positive expression of uPA and uPAR were concentrated in tumor tissues compared with that in the adjacent tissues. The positive rates of uPA and uPAR expressed the tissues were 33.33% and 50.00% in G1 grade; 88.47% and 96.15% in G3 grade; 37.50% and 50.00% in Ta-T1 tissues; 100.0% and 100.0% in T4 tissues, respectively. The positive rates of uPA and uPAR expression in tumor tissues with higher grade and stage were obviously increased (P< 0.05); meanwhile, there were close correlation between uPA and uPAR (rs=0.979). CONCLUSION: The co-expression of uPA and uPAR was one of the characteristics of urinary transitional cell carcinoma and significantly correlated with tumor stage and grade.	bladder
Analysis of local T lymphocyte subsets upon stimulation with intravesical BCG: a model to study tuberculosis immunity.	Cell-mediated immune response can control tuberculosis infection. A significant role for immune cells like CD4, CD8 and gammadelta T lymphocytes have been recognized, but little is known about the kinetics of activation and accumulation of these cells in course of Tuberculosis infection in humans. This is due to both the difficult to access to human lung and the fact that most subjects are examined in different periods of infection which may condition T cell changes. To overcome these problems, we have used intravesical BCG (Bacillus Calmette-Guerin) treatment for preventing the recurrences of bladder cancer as an in vivo experimental model of human tuberculosis infection. 20 male caucasian patients with proven bladder superficial transitional cell carcinoma treated with transurethral resection followed by six weekly intravesical instillations of BCG (T0-T6) were enrolled. Changes in T lymphocyte subsets were assessed by flow cytometry in the bladder wash recovered after each BCG instillation. Our study shows that the action of BCG appears to be T cell dependent. Lymphocytes increase at any new instillation and tend towards the reduction with the suspension of the stimulus. BCG induces a massive increase in the proportion of CD4 Th1 subset followed by an increase in gammadelta T cells, while no significant variation for CD8 and NK cells is found. Our results suggest that BCG infection model represents a valid experimental tool to study the immunological events evoked in vivo by Mycobacterium tuberculosis in humans at the site of infection.	bladder
[Active chemotherapy with gemcitabine, carboplatin and docetaxel for three patients with MVAC-resistant liver metastasis of urothelial carcinoma].	We report three cases with methotrexate-vinblastin-adriamycin-cisplatin (MVAC) resistant multiple liver metastases of urothelial carcinoma that responded to combination chemotherapy consisting of gemcitabine plus carboplatin (GC) with additional docetaxel (GCD) as salvage chemotherapy. Case 1: A 55-year-old man underwent left nephroureterectomy for ureteral cancer (TCC, G3, pT3pN1M0). Three courses of GC followed by three courses of GCD were given via intra-hepatic arterial infusion for multiple liver metastases, which appeared after adjuvant high-dose MVAC therapy. Complete response was obtained and maintained for 11 months. Case 2: A 46-year-old man underwent radical cystectomy for locally advanced bladder cancer (TCC G3 + adenocarcinoma. pT3pN0M0). Two courses of GC followed by 2 courses of GCD systemic therapies were performed for multiple liver metastases, which appeared after adjuvant high-dose MVAC therapy. Partial response was obtained and maintained for six months. Case 3: A 66-year-old man received three courses of MVAC for multiple metastases of the bladder cancer (TCC, G3, > pT2), which resulted in disease progression. Eight courses of GC followed by six courses of GCD were administrated via intra-hepatic arterial infusion. Partial response was obtained and maintained for 12 months. Although the response duration was still short, GC and GCD may be promising salvage chemotherapeutic regimens for the patients with MVAC-resistant liver metastases of urothelial carcinoma.	bladder
[A case of primary choriocarcinoma of the bladder].	A 75-year-old man visited our hospital presenting with gross hematuria. Cystoscopy revealed a bladder tumor with coagulated blood and necrotic tissue at the dome. We resected the bladder tumor transurethrally. Pathologically, the tumor was shown to be a transitional cell carcinoma with choriocarcinomatous differentiation, G3, > or = pT2. Immunohistochemical staining showed human chorionic gonadotropin (HCG)-positive tumor cells. Just after surgery, the serum HCG-beta concentration was less than 0.1 ng/ml. Total cystectomy and an ileal conduit operation were performed. The histological classification was TCC, G3, pTis. In later blood chemistry tests, HCG-beta elevation was observed. Pulmonary metastases appeared on a chest X-ray, and combination chemotherapy with cisplatin and etoposide was administered. Although the serum HCG-beta decreased with one course of chemotherapy, it increased immediately thereafter. The patient died of the disease about 8 months after the total cystectomy. Autopsy revealed multiple metastases in the lungs, liver, kidneys, stomach, pancreas, thyroid gland, adrenal glands, heart, jejunum, and vertebral body (Th10). Lymph node metastases in the pulmonary hilum, mediastinum, and right submaxillary gland were also found.	bladder
[A case of anaphylactic shock induced by pirarubicin hydrochloride].	A 75-year-old man was admitted to our hospital for treatment of superficial bladder tumor. Transurethral resection (TUR) was performed and histopathological examination revealed a transitional cell carcinoma (G2). Despite one course of post-TUR bladder instillation therapy using pirarubicin hydrochloride, carcinoma in situ (CIS) was found 4 months later. CIS disappeared after another course of bladder instillation therapy using BCG; but, it recurred a month later. BCG bladder instillation therapy was performed again, and no malignant cells were detected in the urinary tract thereafter. Four months later, lung metastasis was diagnosed and an MVAC regimen (cisplatin, methotrexate, vinblastin adriamycin) was administered. However, anaphylactic shock was induced by intravenous injection of pirarubicin hydrochloride, so this therapy was stopped in the middle of the second course. Even though the lung metastasis disappeared once after the same MVAC treatment, it recurred the following year. At that time, 3 courses of a cisplatin-methotrexate-vinblastin regimen were administered, and a complete response was achieved.	bladder
Incidence of bladder cancer discovered by urethrocystoscopy at prostate biopsy: extraordinary high incidence of tiny bladder cancer in elderly males.	In order to clarify the incidence of bladder cancer with and without prostate cancer, we investigated bladder cancer discovered incidentally by urethrocystoscopy at prostate biopsy. Between April 1997 and December 2003, 498 patients who were suspected prostate cancer were performed prostate biopsy and urethrocystoscopy simultaneously. We investigate possible invasion of prostate cancer into the urethra or bladder mucosa as well as bladder cancer, including other benign lesions of the bladder by urethrocystoscopy. Prostate cancer was confirmed in 175 (35.1%) of the 498 patients histologically, and bladder cancer was discovered incidentally in 12 patients (2.4 %). The incidence of bladder cancer in patients with prostate cancer of 2.3% (4/175) was not significantly different from that in patients without prostate cancer, which was 2.5% (8/323). Superficial and those with a size less than 1 cm were noted in 11 patients (92%) and 10 patients (83%) respectively. High incidence rate of bladder cancer with prostate cancer was reported previously, however, there was no study to compare the incidence rate of bladder cancer between cases with and without prostate cancer. The present study suggests that asymptomatic tiny bladder cancer may be present at an unexpectedly high incidence rate in elderly males.	bladder
Expression of cathepsins B, H, and L and their inhibitors as markers of transitional cell carcinoma of the bladder.	OBJECTIVES: It has been shown that the expression of the lysosomal proteolytic enzymes cathepsin B, H, and L (CB, CH, and CL, respectively) correlate with tumor progression in various neoplasms. However, no data are available in cell lysates and supernatants of differently differentiated human bladder cell lines or in noncancerous and cancerous bladder tissue. METHODS: Using spectrofluorometric assays, catalytic activities of CB, CH, CL, and their inhibitor (CIP) were measured both in differently differentiated human bladder cell lines (HCV29, normal; RT4, well differentiated; J82, poorly differentiated) and in noncancerous and cancerous tissue samples (n = 20) of transitional cell carcinoma obtained from transurethral resections of the bladder or cystectomies. Enzyme activities were related to the protein content in tissue samples or to the cell count in cell lines. RESULTS: In comparison to the intracellular activities of CB, CH, and CL in the poorly differentiated cell line J82, the intracellular activities in the normal cell line HCV29 were significantly greater (P <0.05), independent of stage or grade. In contrast, the portion of cathepsins released from cell line J82 into the supernatant revealed higher values than that from cell line HCV29. In cancerous bladder tissue, CB and CH were significantly greater than in the matched normal tissue (P <0.05). CL and CIP did not show any statistically significant differences. CONCLUSIONS: Increased cathepsin concentrations in the supernatant of the poorly differentiated J82 carcinoma cell culture, as well as in cancerous bladder tissue, are indicative of a proteolytic imbalance and potential indicators of bladder cancer.	bladder
Long-term effects of bacille Calmette-Guérin perfusion therapy for treatment of transitional cell carcinoma in situ of upper urinary tract.	OBJECTIVES: To report our experience with bacille Calmette-Guérin (BCG) perfusion therapy for transitional cell carcinoma in situ of the upper urinary tract. BCG perfusion therapy is widely used to treat transitional cell carcinoma in situ of the upper urinary tract. However, it has not yet been established as a standard treatment. METHODS: Ten patients diagnosed with transitional cell carcinoma in situ of the upper urinary tract were treated with BCG perfusion therapy from January 1990 to May 2002. BCG was instilled weekly for 6 weeks, with a median dose of 65 mg at 1.17 mg/mL (Tokyo 172 strain, dissolved in normal saline). RESULTS: The mean follow-up period was 50.9 months (range 12 to 134). The initial response to therapy was excellent, and cytology became negative in all patients after one course of BCG perfusion. Five patients developed recurrence after 5, 11, 24, 26, and 45 months, and all died after 46, 12, 41, 134, and 79 months, respectively. The mortality rate was 50% and was 100% in those with recurrence. The mean recurrence-free period was 22.2 months (range 5 to 45). Complications included bladder irritation-related symptoms in all patients, fever greater than 38 degrees C (n = 9), hematuria (n = 2), hydronephrosis (n = 2), and lumbago (n = 1) but all were transient and did not affect long-term prognosis. CONCLUSIONS: BCG perfusion therapy for carcinoma in situ of the upper urinary tract is safe, and the short-term response is excellent. However, the long-term results were not satisfactory. Therefore, this therapy should be considered experimental, although it may have potential benefits in delaying progression and possibly providing local control for patients in poor condition. Long-term studies are required for additional evaluation of BCG therapy.	bladder
Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome.	OBJECTIVE: To determine the ability of pathologists to reproducibly diagnose a newly defined lesion, i.e. the papillary urothelial neoplasm of low malignant potential (PUNLMP) using the published criteria, defined by the 1998 World Health Organisation/International Society of Urological Pathology (WHO/ISUP) classification system; in addition, debate remains about the clinical behaviour of these lesions, thus the rates of recurrence and progression of PUNLMP lesions were assessed and compared with low-grade papillary urothelial carcinomas (LG-PUC) and high-grade (HG-PUC) over a 10-year follow-up. PATIENTS AND METHODS: Forty-nine cases of superficial bladder cancer (G1-3 pTa) representing an initial diagnosis of transitional cell carcinoma made in 1990 were identified and re-graded using the 1998 WHO/ISUP classification by two pathologists. Inter-observer agreement was assessed using Cohen weighted kappa statistics. After re-classification the clinical follow-up was reviewed retrospectively, and episodes of recurrence and progression recorded. RESULTS: The inter-observer agreement was moderate, regardless of whether one (kappa 0.45) or two (kappa 0.60) pathologists were used to grade these lesions. Re-classification identified 12 PUNLMP, 28 LG-PUC and nine HG-PUC. PUNLMP lesions recurred in 25% (3/12) of cases; no progression was documented. Recurrence rates were 75% (21/28) and 67% (6/9) for LG- and HG-PUC, respectively, and progression rates were 4% (1/28) and 22% (2/9). CONCLUSION: The 1998 WHO/ISUP classification of urothelial neoplasms can be reproducibly applied by pathologists, with a moderate level of agreement. There is evidence that PUNLMP lesions have a more indolent clinical behaviour than urothelial carcinomas. However, the risk of recurrence and progression remains, and clinical monitoring of these patients is important.	bladder
Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification.	The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer.	bladder
Impact of proteomics on bladder cancer research.	Detecting bladder cancer at an early stage and predicting how a tumor will behave and act in response to therapy, as well as the identification of new targets for therapeutic intervention, are among the main areas of research that will benefit from the current explosion in the number of powerful technologies emerging within proteomics. The purpose of this article is to briefly review what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate the translation of basic discoveries into the daily clinical practice.	bladder